Cloning and characterization of the t(15;17) translocation breakpoint region in acute promyelocytic leukemia.
A reciprocal chromosomal translocation, t(15;17)(q22;q11.2-12), is characteristic of acute promyelocytic leukemia (APL) of French-American-British (FAB) subtype M3, and is not associated with any other human malignancy. The non-random pattern of the APL translocations suggests that specific genes on chromosomes 15 and 17 are somehow altered or deregulated as a consequence of the rearrangement. Translocation breakpoints in APL patients provide physical landmarks that suggest an approach to isolating the APL gene(s). Genetic and physical maps constructed for the APL breakpoint region on chromosome 17 have indicated that two fully-linked DNA markers, defining loci for THRA1 and D17S80, map to opposite sides of an APL breakpoint yet reside on a common 350-kb Clal fragment. Cosmid-walking experiments to clone this APL breakpoint have revealed a 38-kilobase deletion on chromosome 17. Studies in additional APL patients have shown that the breakpoint region on chromosome 17 spans at least 80 kilobases.
Lemons
R S
RS
Department of Pediatrics, Howard Hughes Medical Institute, Salt Lake City, Utah.
Eilender
D
D
Waldmann
R A
RA
Rebentisch
M
M
Frej
A K
AK
Ledbetter
D H
DH
Willman
C
C
McConnell
T
T
O'Connell
P
P
D016386:Chromosome Walking; D002884:Chromosomes, Human, Pair 15 / Q000648:ultrastructure*; D002886:Chromosomes, Human, Pair 17 / Q000648:ultrastructure*; D003360:Cosmids; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D009857:Oncogenes; D014178:Translocation, Genetic
D015342:DNA Probes; D004273:DNA, Neoplasm; D005819:Genetic Markers